2,357 research outputs found

    Exploiting entanglement in communication channels with correlated noise

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    We develop a model for a noisy communication channel in which the noise affecting consecutive transmissions is correlated. This model is motivated by fluctuating birefringence of fiber optic links. We analyze the role of entanglement of the input states in optimizing the classical capacity of such a channel. Assuming a general form of an ensemble for two consecutive transmissions, we derive tight bounds on the classical channel capacity depending on whether the input states used for communication are separable or entangled across different temporal slots. This result demonstrates that by an appropriate choice, the channel capacity may be notably enhanced by exploiting entanglement.Comment: 9 pages, 5 figure

    Characterization of the non-classical nature of conditionally prepared single photons

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    A reliable single photon source is a prerequisite for linear optical quantum computation and for secure quantum key distribution. A criterion yielding a conclusive test of the single photon character of a given source, attainable with realistic detectors, is therefore highly desirable. In the context of heralded single photon sources, such a criterion should be sensitive to the effects of higher photon number contributions, and to vacuum introduced through optical losses, which tend to degrade source performance. In this paper we present, theoretically and experimentally, a criterion meeting the above requirements.Comment: 4 pages; 3 figure

    Social networks : the future for health care delivery

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    With the rapid growth of online social networking for health, health care systems are experiencing an inescapable increase in complexity. This is not necessarily a drawback; self-organising, adaptive networks could become central to future health care delivery. This paper considers whether social networks composed of patients and their social circles can compete with, or complement, professional networks in assembling health-related information of value for improving health and health care. Using the framework of analysis of a two-sided network – patients and providers – with multiple platforms for interaction, we argue that the structure and dynamics of such a network has implications for future health care. Patients are using social networking to access and contribute health information. Among those living with chronic illness and disability and engaging with social networks, there is considerable expertise in assessing, combining and exploiting information. Social networking is providing a new landscape for patients to assemble health information, relatively free from the constraints of traditional health care. However, health information from social networks currently complements traditional sources rather than substituting for them. Networking among health care provider organisations is enabling greater exploitation of health information for health care planning. The platforms of interaction are also changing. Patient-doctor encounters are now more permeable to influence from social networks and professional networks. Diffuse and temporary platforms of interaction enable discourse between patients and professionals, and include platforms controlled by patients. We argue that social networking has the potential to change patterns of health inequalities and access to health care, alter the stability of health care provision and lead to a reformulation of the role of health professionals. Further research is needed to understand how network structure combined with its dynamics will affect the flow of information and potentially the allocation of health care resources

    Hepatitis C virus vaccine: Challenges and prospects

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated

    Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes

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    Anti-hepatitis C virus (HCV) cross-neutralizing human monoclonal antibodies, directed against conserved epitopes on surface E2 glycoprotein, are central tools for understanding virus-host interplay, and for planning strategies for prevention and treatment of this infection. Recently, we developed a research aimed at identifying these antibody specificities. The characteristics of one of these antibodies (Fab e20) were addressed in this study. Firstly, using immunofluorescence and FACS analysis of cells expressing envelope HCV glycoproteins, Fab e20 was able to recognize all HCV genotypes. Secondly, competition assays with a panel of mouse and rat monoclonals, and alanine scanning mutagenesis analyses located the e20 epitope within the CD81 binding site, documenting that three highly conserved HCV/E2 residues (W529, G530 and D535) are critical for e20 binding. Finally, a strong neutralizing activity against HCV pseudoparticles (HCVpp) incorporating envelope glycoproteins of genotypes 1a, 1b, 2a, 2b and 4, and against the cell culture-grown (HCVcc) JFH1 strain, was observed. The data highlight that neutralizing antibodies against HCV epitopes present in all HCV genotypes are elicited during natural infection. Their availability may open new avenues to the understanding of HCV persistence and to the development of strategies for the immune control of this infection

    A Prograding Margin during Global Sea-Level Maxima: An Example from Mahajanga Basin, Northwest Madagascar

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    The Mesozoic shelf margin in the Mahajanga Basin, northwest Madagascar, provides an example where inherited palaeobathymetry, coupled with sea-level changes, high sediment supply and fluctuations in accommodation influenced the stacking patterns and geometry of clinoforms that accreted onto a passive rifted margin. Two-dimensional (2D) seismic profiles are integrated with existing field data and geological maps to study the evolution of the margin. The basin contains complete records of transgression, highstand, regression and lowstand phases that took place from Jurassic to Cretaceous. Of particular interest is the Cretaceous, Albian to Turonian (ca. 113-93 Ma), siliciclastic shelf margin that prograded above a drowned Middle Jurassic carbonate platform. The siliciclastic phase of the shelf margin advanced ca. 70 km within ca. 20 My, and contains 10 distinct clinoforms mapped along a 2D seismic reflection data set. The clinoforms show a progressive decrease in height and slope length, and a fairly constant slope gradient through time. The successive shelf edges begin with a persistent flat to slightly downward-directed shelf-edge trajectory that changes to an ascending trajectory at the end of clinoform progradation. The progressive decrease in clinoform height and slope length is attributed to a decrease in accommodation. The prograding margin is interpreted to have formed when siliciclastic input increased as eastern Madagascar was uplifted. This work highlights the importance of sediment supply and inherited palaeobathymetry as controls on the evolution of shelf margins and it provides a new understanding of the evolution of the Mahajanga Basin during the Mesozoic

    The past, present and future of neutralizing antibodies for hepatitis C virus

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    Hepatitis C virus (HCV) is a major cause of liver disease and hepatocellular carcinoma worldwide. HCV establishes a chronic infection in the majority of cases. However, some individuals clear the virus, demonstrating a protective role for the host immune response. Although new all-oral drug combinations may soon replace traditional ribavirin–interferon therapy, the emerging drug cocktails will be expensive and associated with side-effects and resistance, making a global vaccine an urgent priority. T cells are widely accepted to play an essential role in clearing acute HCV infection, whereas the role antibodies play in resolution and disease pathogenesis is less well understood. Recent studies have provided an insight into viral neutralizing determinants and the protective role of antibodies during infection. This review provides a historical perspective of the role neutralizing antibodies play in HCV infection and discusses the therapeutic benefits of antibody-based therapies. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.

    Novel functional hepatitis C virus glycoprotein isolates identified using an optimised viral pseudotype entry assay

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    Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, pre-clinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from individual patient quasispecies were discovered to behave very differently in this entry model. Empirical optimisation of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterised as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) were also sensitive to the amount, and ratio, of plasmids used, and that protocols for optimal production of these pseudoviruses is dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilising pseudoviruses to conduct empirical optimisation of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping

    Flexible and rapid construction of viral chimeras applied to Hepatitis C Virus

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    A novel and broadly applicable strategy combining site directed mutagenesis and DNA assembly for constructing seamless viral chimeras is described using Hepatitis C Virus as an exemplar. Full-length HCV genomic cloning cassettes, which contained flexibly situated restriction endonuclease sites, were prepared via a single site-directed mutagenesis reaction and digested to receive PCR amplified virus envelope genes by In-Fusion cloning. Using this method we were able to construct gene-shuttle cassettes for generation of cell culture-infectious JFH-1-based chimeras containing genotype 1-3 E1E2 genes. Importantly, using this method we also show that E1E2 clones that were not able to support cell entry in the HCV pseudoparticle assay did confer entry when shuttled into the chimeric cell culture chimera system. This method can be easily applied to other genes of study and other viruses and, as such, will greatly simplify reverse genetics studies of variable viruses

    Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

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    Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells
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